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However, the utility of genetic testing in risk stratification remains poorly characterised.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To examine the influence of genetic risk on advanced fibrosis and cirrhosis in patients with type 2 diabetes mellitus (T2DM) and the utility of a polygenic risk score (PRS) in screening guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We prospectively enrolled adults aged \u226550\u2009years with T2DM recruited from clinics. PRS was the sum of risk alleles in <jats:italic>PNPLA3<\/jats:italic>, <jats:italic>TM6SF2<\/jats:italic> and <jats:italic>SERPINA1<\/jats:italic> minus the protective variant in <jats:italic>HSD17B13<\/jats:italic>. We performed magnetic resonance elastography and vibration\u2010controlled transient elastography to assess for advanced fibrosis and cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 382 included patients, the mean age and BMI were 64.8 (\u00b18.4) years and 31.7 (\u00b16.2)\u2009kg\/m<jats:sup>2<\/jats:sup> respectively. The prevalence of advanced fibrosis and cirrhosis were 12.3% and 5.2% respectively; higher PRS was associated with increased risk of cirrhosis (2.7% vs. 7.5%, <jats:italic>p<\/jats:italic>\u2009=\u20090.037). High PRS was associated with increased risk of advanced fibrosis among those with fibrosis\u20104 index (FIB\u20104) index &lt;1.3 (9.6% vs. 2.3%, <jats:italic>p<\/jats:italic>\u2009=\u20090.036) but was not significantly different in other FIB\u20104 categories. Incorporating PRS determination into the American Gastroenterological Association and American Association for the Study of Liver Diseases screening guidelines prevented approximately 20% of all participants with advanced fibrosis from being inappropriately classified as low risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Utilising a well\u2010phenotyped, prospective cohort of adults with T2DM, we found that adding an assessment of genetic risk to recommendations to screen at\u2010risk populations may improve risk prediction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.18099","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T06:34:33Z","timestamp":1717396473000},"page":"369-377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The impact of genetic risk on the prevalence of advanced fibrosis and cirrhosis in prospectively assessed patients with type 2 diabetes"],"prefix":"10.1111","volume":"60","author":[{"given":"Lana","family":"Bridi","sequence":"first","affiliation":[{"name":"MASLD Research Center, Division of Gastroenterology University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saaket","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"},{"name":"Division of Cardiology Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaleb","family":"Tesfai","sequence":"additional","affiliation":[{"name":"MASLD Research Center, Division of Gastroenterology University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egbert","family":"Madamba","sequence":"additional","affiliation":[{"name":"MASLD Research Center, 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